Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• backbone modification is compatible with the preservation of its typical membrane leakage and antibiotic properties, although somewhat attenuated. Keywords: bioactivity; conformation; peptaibiotic; peptide synthesis; peptides; thiopeptides; Introduction Since their first incorporation into peptides [1

• -dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG) model membrane was exploited. The extent of permeation induced by the three analogues is similar, although 30–40% lower than that of the parent peptaibiotic. The antimicrobial activities were assessed on a large set of Gram-positive and Gram-negative

• . aureus are comparable, but reduced by about 40% with respect to that of the parent peptaibiotic. Conclusion In this work, we performed a partial thioamide scan of the short lipopeptaibiotic [Leu11-OMe] trichogin GA IV by synthesizing and studying three thioamide-containing analogues. The syntheses were